The long term goals of this program include the laboratory synthesis of complex natural products possessing desirable biological activity as well as the development of new synthetic methodology that will simplify this task. In addition, we plan to attempt to identify, and to synthesize and test, analogs of these naturally occurring lead compounds which can be accessed synthetically in a more practical manner than the natural compounds themselves. Ongoing investigations on the total synthesis of the complex cytotoxic macrodiolide swinholide will be continued and hopefully brought to completion, as will studies on the promising compound epothilone, which has activity similar to that of taxol. Our studies on the potent and extremely promising anticancer agent bryostatin 1 will continue, and we hope to expand this program aggressively into analog synthesis. Syntheses of leucascandrolide and dolabelide B will be initiated, and analogs of leucascandrolide will be prepared for assay as antifungal and cytotoxic agents. Throughout all of this work, we hope to implement new organic reactions and synthetic strategies which will facilitate the construction of the targeted compounds, as well as prove useful in a broader context.